SIGMA-RECEPTOR BINDING-AFFINITY AND INHIBITION OF APOMORPHINE-INDUCEDCLIMBING

Several relatively selective compounds with affinity for the sigma bin ding site were assessed for their ability to inhibit apomorphine-induc ed climbing in the mouse. Although, the majority of compounds inhibite d apomorphine-induced climbing, there was no correlation between the a bility to inhibit climbing and potency in sigma binding assays using [ H-3]1,3-di-o-tolylguanidine (DTG) or [H-3](+)-pentazocine as ligands. The potency of the compounds to inhibit binding to muscarinic M1 or M2 receptors correlated with the potency to inhibit apomorphine-induced climbing. However, several of the compounds that inhibit climbing had muM affinity at muscarinic receptors. Whether these concentrations wer e achieved in vivo is unclear. Our data suggest that sigma activity pe r se is not responsible for inhibition of apomorphine-induced climbing .